The disclosure of the present application relates generally to vessel and heart efficiency and risk of disease. More particularly, the disclosure of the present application relates to techniques for evaluating cardiovascular function.
Many cardiovascular diseases, including diabetes, hypertension, and heart failure, have impaired arterial vasoactivity, namely vasoconstriction and vasodilation. Hypertension, for example, is associated with changes in vasomotor tone and typically attenuates vasodilation. The vasoactivity may also be altered under physiological conditions, such as in normal growth, exercise, etc. The regulation of the vasomotor tone in medium-sized arteries is of particular interest because of the clinical relevance to vasospasm and atherosclerosis.
In addition to the active component (vasoactivity) of blood vessels, there is great interest in the elasticity of vessels. One of the reasons for the great interest stems from the observation that increased stiffness of large elastic arteries represents an early risk factor for cardiovascular diseases. Specifically, increased aortic stiffness is associated with aging, hypertension, diabetes, hyperlipidemia, atherosclerosis, heart failure, and smoking. Furthermore, arterial stiffness has also been shown to be an independent risk factor for cardiovascular events such as primary coronary events, stroke, and mortality. Therefore, the assessment of the passive and active mechanical properties of vessels is particularly important for understanding the mechanisms of cardiovascular disease.
Clinically, the compliance or stiffness of blood vessels is used as an index of vascular mechanics, and hence, vessel function. These measurements can be made from imaging (e.g., ultrasound) to obtain the deformation (change of dimension) and loading (pressure). The endothelial function is typically measured by the degree of vasodilation or reactive hyperemia (namely the change of diameter from imaging) post cuff occlusion. Unfortunately, these measurements can be quite variable and the theoretical basis for the measurements is not well founded. Hence, there is a need to determine a theoretically-based parameter that quantifies the function of blood vessels.
Regarding the heart, much effort has gone into quantifying myocardial function, independent of ventricular loading conditions. In the left ventricle (LV), the peak first time-derivative of LV intracavitary pressure, dP/dtmax, is a sensitive cardiac index of inotropicity and the current detection ‘gold standard.’Currently, the ability to obtain an accurate determination of dP/dtmax requires measurement of intraventricular LV pressure using invasive cardiac catheterization. In general, it is very difficult to accurately assess ventricular pressure non-invasively.
An additional difficulty with LV dP/dtmax is that it is not preload-independent. Conceivably, LV pressure-volume relationship and elastance reflect LV contractile function more accurately formalized as the time-varying elastance of the ventricle, by defining elastance, E. Elastance is defined as E(t)=P(t)/(V(t)−Vd), where P(t) and V(t) are ventricular pressure and volume that vary with time (t), respectively. Vd is the LV volume corresponding to zero LV pressure obtained by drawing a tangent to the pressure-volume curves at the end-ejection.
It has been shown that the end-systolic pressure volume (ESPV) relationship, which is the loci of pressure and volume points at end-systole, is insensitive to variations of both the end-diastolic volume (preload) and the mean arterial pressure (afterload). The ESPV relationship is usually a straight line with a slope of Ees. It is found that Ees remains essentially constant if the preload and afterload are allowed to vary within the physiologic range, but is sensitive to inotropic agents and ischemia. Hence, Ees has been proposed as a “load independent” index of contractility of the ventricle. Elastance measures also require cardiac catheterization for measurement of pressure which further reduces their clinical utility. An additional limitation of Ees is that it is not easy to change afterload and obtain multiple pressure-volume data points in a given subject while maintaining a constant contractility. As such, it is impractical to use Ees clinically for patient-specific LV catheterization-ventriculography data. Hence, there is a need for a cardiac index that is more readily accessible and practical.